Thebaine is an opiate alkaloid. While thebaine is not used therapeutically itself, it can be converted industrially into a variety of therapeutically important opiate alkaloids including oxycodone, oxymorphone, nalbuphine, naloxone, naltrexone, diprenorphine, buprenorphine and etorphine. Buprenorphine, for example, is a thebaine derivative with powerful analgesia approximately twenty-five to forty times as potent as morphine, and is indicated for the treatment of moderate to severe chronic pain or for pre-operative analgesia. Buprenorphine is also used to treat opiate addiction.
Buprenorphine is generally made via a synthetic route that starts with thebaine or oripavine undergoing a cycloaddition reaction, which is then followed by a hydrogenation reaction. The resultant ketone, 1-[(5α,7α)-4,5-epoxy-18,19-dihydro-3,6-dimethoxy-17-methyl-6,14-ethenomorphinan-7-yl]-ethanone, undergoes an addition reaction in which a tertiary butyl group is added to the C7 acetyl group to produce α-(1,1-dimethylethyl)-4,5-epoxy-18,19-dihydro-3,6-dimethoxy-α,17-dimethyl-6,14-ethenomorphinan-7-methanol. This addition reaction is inefficient because some of the product that is formed is converted back to the starting material, which is then discarded during the subsequence work up procedure. Since this addition reaction is an early step in the synthesis of buprenorphine and the yield of this step is low, it contributes significantly to the low overall yield of the buprenorphine synthesis process. A need therefore exists for a process that increases the yield of this addition step in the synthesis of buprenorphine and related opiate alkaloids.